The product of open reading frame 14 (orft4) of herpesvirus saimiri (HVS) exhibits significant homology with mouse mammary tumor virus superantigen orfl4 encodes a 50-kDa secreted glycoprotein, as shown previously (Z Yao, E Maraskovsky, M K Spriggs, J I Cohen, R J Armitage, and M R Alderson, J Immunol 156:3260-3266, 1996) orfl4 expressed from recombinant baculovirus powerfully induces proliferation of CD4-positive cells originating from several different species To study the role of orfl4 in transformation, a mutant form of HVS (HVS orfl4) was constructed with a deletion in the orfl4 gene The transforming potential of HVS orfl4 was tested in cell culture and in common marmosets Parental HVS subgroup C strain 488 immortalized common marmoset T lymphocytes in vitro to interleukin-2-independent growth, while the HVS orft4 mutant did not produce such a growth transformation In addition, HVS orfl4 was nononcogenic in common marmosets In contrast to oth er nononcogenic HVS mutant viruses which were repeatedly isolated from peripheral blood mononuclear cells of infected marmosets for more than 5 months, HVS orfl4 did not persist at a high level in vivo These results demonstrate that orfl4 of HVS is not required for replication but is required for transformation and for high-level persistence in vivo PUBLICATIONS Duboise, SM, Guo, J, Czajak, S, Lee, H, Veazey, Desrosiers, RC and Jung, JU A role for herpesvirus saimiri orf14 in transformation and persistent infection J Virol 1998; 72:6770-6776